<P>We have developed an immunotoxin SS1P that targets ovarian cancers, mesotheliomas and pancreatic cancers that is currently in clinical trials. We are carrying out laboratory experiments to produce improved forms of SS1P that are less immunogenic so that several treatment cycles can be given. We have also investigated how to improve the activity of SS1P against solid tumors and found that if chemotherapy is give before SS1P there is profound synergy. We are investigating the mechanism of this synergy.</p><p>We have studied mesothelin expression in lung cancer and demonstrated lung cancer cells are good targets for SS1P therapy.</p><p>We have developed a new method of displaying Fvs on the surface of human cells and used this method to isolate new high affinity antibodies that react with CD22 and mesothelin.</p><p>We prepared a new immunotoxin targeting a stem cell antigen on leukemias and showed it rapidly killed leukemia cells expressing CD123.</P><P><U>Hematopoietic Tumors</U>- Immunotoxin BL22 has shown excellent clinical activity in patients with Hairy Cell Leukemia. To increase the usefulness of BL22 in other leukemias and lymphomas we have mutated the protein to increase its affinity for CD22 and also mutated the toxin to increase its ability to reach the cytosol and kill target cells. An improved form of BL22 called HA22 has been licensed to Cambridge Antibody Technology who will sponsor trials in various B cell leukemias and lymphomas. Other high affinity forms of BL22 are now being prepared.</P>